How Ovaries Influence More Than Just Reproduction with Dr. Piraye Beim

How Ovaries Influence More Than Just Reproduction with Dr. Piraye Beim
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Dr. Beim: But it turns out the ovary is a metabolic organ. It's an immune organ. It's an endocrine organ. It signals to virtually every other cell, every other tissue in the body. And it's also a very complicated organ itself. It's a very complicated tissue, and it's one that we're just now starting to understand.

Dr. Beim: And so our ovarian function is not aligned. with the modern human lifespan.

Dr. Taz: Right.

Dr. Beim: You've made me not feel

Dr. Taz: insane. I don't know how many times I've had these conversations. It's not all in your head. I know. I feel so validated right now. So thank you. Awesome. There's not a day that goes by in practice where I don't sit with a woman who is either struggling to get pregnant, not clear on why she went into an early perimenopause or menopause, or just feels pressured quite honestly to hurry up and have a child because her eggs are going to run out.

Dr. Taz: or her time is up. And oftentimes that haste leads to waste and really wrong decisions. That's why I wanted to bring on my next guest. I want you guys to meet Dr. Bime. She is rethinking reproductive health, fertility, early menopause, premature menopause, perimenopause, all the things, because she's talking about ovarian health and how we that advocate for women's health.

Dr. Taz: Really need to be talking more about the field of ovarian health and what we can and cannot do to protect our ovaries and to really innovate our ovaries. So they're working for us, not against us, maybe even extending the timeline so that we are no longer in a rush to have children. Let me tell you a little bit about Dr.

Dr. Taz: Byam. She is an avid researcher. She's a biologist. She's been in women's health for over 20 years, and she's done a lot of PhD work innovating precision medicine. for different areas of women's health. She founded her company cell Maddox as an opportunity to really focus on reproduction and reproductive equity for women, including novel drugs that extend ovarian age and actually help decrease the need for things like assisted reproductive technology.

Dr. Taz: She's been a member of the ask. Global leadership network. She was named to cranes 40 under 40. She's a notable woman in tech, according to Goldman Sachs. And she's a top 15 founder and fortune, and she is rock health disruptive founder of the year. I'm pleased honored. Thrilled to welcome Dr. Bime to the show to help us understand ovarian health and what the future of reproduction, perimenopause, and menopause is going to look like.

Dr. Taz: Dr. Bime, thrilled to have you on the show. You have been an advocate, a champion of this whole idea around ovarian health. Separate, but under the category of women's health. And I'm fascinated by that because, you know, with the work that I do, we do take that into account but we think of it more to be 100 percent honestly in terms of like data and numbers and hormone levels and estrogen and testosterone and all this business.

Dr. Taz: So talk to us a little bit about ovarian health and what that means to you and why you think it needs to be its own category.

Dr. Beim: So thanks for having me on today. I'm excited to have this conversation. Um, my background is as a biologist. So I'm a PhD biologist and, um, one who specialized in medical science for many years.

Dr. Beim: And about 15 years ago, I started my journey with Cellmatics, which is my company that I founded and I run today as CEO. Um, but I've been innovating in women's health for over 20 years as a scientist. And when I founded Cellmatics, We had a very straightforward question, which was actually quite radical, which is we know that women have different body parts.

Dr. Beim: We know that we have different chromosomes in our DNA and genes that underlie those different body parts. But what does it really mean to be female biologically on a cellular level that helps us understand why women get certain diseases that men don't get or are disproportionately protected from certain diseases?

Dr. Beim: or disproportionately impacted by certain diseases, so. So

Dr. Taz: what led you even to that question? Like, when we talk about what does it mean to be female, right? You're opening up a whole can of worms right there. Oh, sure. And I don't mean, I don't mean the gender lens. Right, exactly. I'm really just

Dr. Beim: looking at it as a pure cell biologist.

Dr. Beim: What does that mean to a cell to be female?

Dr. Taz: So, tell us about that. Like, what, what does it mean to be a female cell. Like what does that, what does that mean? I actually have never thought of, thought of cells that way. So this is new for me too, but go ahead. Tell me what that means. Well, you're

Dr. Beim: not alone because the pharmaceutical industry has been treating us as male cells.

Dr. Beim: It's kind of tiny males. Yeah. But the reality is that we have. Different cells that are biologically different and that underlies why we get certain conditions and, and, you know, are protected from others. And so we set out to try to understand that and, and what I will say to summarize 15 years of, um, you know, tens of millions of dollars of research and AI and analysis is that the loudest signal that came out of it was the ovary, which makes sense because it is the organ.

Dr. Beim: that determines our sex at birth. So it is a gonad. I had this conversation with someone the other day and they said, wait, ovaries are gonads? And I said, yeah. Ovaries are gonads, yeah. They are gonads. Testes are not the only gonads. And so, um, so it, it was surprising and yet also makes sense that the, at the end of the day, when we, when we think about the unique biology that really determined so much of our health and wellness.

Dr. Beim: Um, the ovaries it turns out sit at the center of that. And, and this was a radical mind shift for me because I was trained as a reproductive biologist. Right. And that's how I self identified. I saw menopause as a natural phenomenon, one that gives us grandmothers. That's a positive adaptation. That's, you know, a special thing humans get to do.

Dr. Beim: Um, I saw the ovary. It's named as the home of the egg, right? So ovary means home of the oocyte, of the ovum. Um, I always saw it as that. I saw the ovary is just this kind of structural thing that houses these magical cells, the eggs. And yet, when we took a step back and we really tried to understand, let's call it female biology, and we're gonna go in the biology zone right now because I understand that these are, you know, difficult topics to navigate for, for a variety of reasons.

Dr. Beim: But they're, they're

Dr. Taz: difficult and there's a lot of bigger words with them and all that other stuff, but they're really important. We have to talk about women are struggling, right? Yes. They're really struggling. And I could share a million stories about women who feel like they have to hurry up and get married or hurry up and do IVF or hurry up and do all these different things.

Dr. Taz: Yeah. Because they're on this, Yeah. And their time's up, you know, and that kind of translates into the same conversation around perimenopause and menopause, the ovary in some way, to be honest, is defining our sort of identity as women, right? Because when ovarian function goes down, then we enter perimenopause and menopause, and then we're struggling with, you know, kind of all these different feelings around that.

Dr. Taz: So this is, this is important, you know, even though it's biology and technical. I hope, I'm hoping everybody watching and listening will pay attention for just a second so that they can kind of follow through the impact of some of this when it comes to even our mental health and just how we present the world.

Dr. Beim: I think that's right. And I think you're pointing out a really important distinction and it's, it's something that I'm still struggling to fully articulate, but it's not that when you don't have an ovary, you're not female. Right. I'm not saying that. What I'm saying is that. When we think of female biology, meaning the biology that disproportionately impacts women who are born with ovaries in a certain way.

Dr. Beim: the reality is that you cannot take the ovary out of the story. And so as a biologist who's trying to understand what makes our bodies unique so that we can then create purpose built solutions for women, pharmaceutical or otherwise, it could be lifestyle interventions. It could be supplements. I'm, I'm just saying in general, when we're trying to give women the protocols, the tools, the, the recommendations and personalize it for them.

Dr. Beim: What the biggest signal that came out of the research that we did over a decade was you can't take the ovary out of the story. Most people associate ovaries with babies and they're clearly very important because they are a reproductive organ also. But it turns out the ovary is a metabolic organ. It's an immune organ.

Dr. Beim: It's an endocrine organ. It, it signals to virtually every other cell. every other tissue in the body. And it's also a very complicated organ itself. So it's not that it's just this like, um, you know, home of the egg.

Dr. Taz (2): Right.

Dr. Beim: It's a very complicated tissue, and it's one that we're just now starting to understand.

Dr. Beim: So, getting to your original question about ovarian health. Yeah. As an innovator in the space, I was struggling to Explain in particular to investors what it was that we were doing and why? And I was finding that I was having to spend half of my investor pitch as an entrepreneur Showing anatomical images to investors, male or female and educating them.

Dr. Beim: It was often the females that I'd spend more time with on this topic because they were fascinated to learn about their bodies. Um, but we'd have to say, this is the ovary. It's a complicated organ. It has an egg in it, but it does a lot more than that. And, um, and so at some point we said, if we look at the evolution of femtech, Once that term was defined.

Dr. Beim: Suddenly, the field took off because then you could identify as a femtech entrepreneur. You're a femtech company. It's a femtech product. You're a femtech investor. You're a femtech fund. And we realized that women's health encompasses so many different categories that when you self identify as an entrepreneur and you're saying, I'm doing women's health within pharma, within drug development, what that meant to everybody was like, okay, well, what are you doing with estrogen?

Dr. Beim: Because that's basically been all we hear about. That's all we hear about. And estrogen is one of the important gonadal hormones. I'm calling it a gonadal hormone because we not an ovarian hormone. Testes make it to postmenopausally women have less estrogen than men. Right. So I know I'm preaching to the choir with you, but for your audience, um, Estrogen is an important gonadal hormone, certainly important for the ovary, but it's the tip of the iceberg.

Dr. Beim: Right. Estrogen, testosterone, progesterone, these are the tip of the iceberg of the factors that are produced by the ovary. And so we had this aha moment and we said, wait. If we define this novel category, and this was about six years ago, if we define this novel category of ovarian health and start identifying as we're an ovarian health company, we're innovating in ovarian health, it does two things.

Dr. Beim: One, it makes people stop and ask, well, what do you mean by ovarian health? Why aren't you just identifying as a reproductive health company or a women's health company? And the second thing it does is in the name, it implies that the ovaries should be healthy.

Dr. Taz: Right. And I love that. And you mentioned that ovarian health is a metabolic endocrine immune organ.

Dr. Taz: Do you mind just drawing some of those pathways for us? Just so for people watching and listening that kind of sinks in for a second about why this is not just about estrogen and why it's not just about getting pregnant.

Dr. Beim: That's right. So, um, Most people are aware that the ovaries are related to babies and increasingly people are becoming aware that it's an endocrine organ So it's important for these hormones That are in our bodies.

Dr. Beim: What people don't understand is that The ovary is very important for things like immune function. Mm hmm. So inflammation is, is a buzzword today. We hear about inflammation, but there's local inflammation and chronic inflammation. And the analogy that I like to make is to music. So, if you and I are having this conversation right now, if there was a fog horn going on in the background, we wouldn't be able to hear ourselves, right?

Dr. Beim: So, um, ovulation, which is when a follicle bursts and an egg comes out, um, ovulation is an inflammatory process. Menstruation. when you get your period is an inflammatory process. Implantation of an embryo into a uterus at the beginning of a pregnancy being set up is an inflammatory process. These are productive inflammatory processes that are necessary for certain functions in our body.

Dr. Beim: But then we have We have peripheral inflammation to this is the inflammatory mechanism that says, Oh, we have a infection. For example, let's go to the site of infection and let's neutralize this virus. A lot of aspects of aging and also the modern lifestyle that many of us kind of, you know, have. end up contributing to those systemic inflammatory signals and they never get resolved.

Dr. Beim: When you have a infection, you go, you have your systemic inflammation, you resolve the infection, you come back down to baseline. But a lot of aspects of aging and also, um, the modern lifestyle mean that that systemic inflammation never calms down. And so what ends up happening is it ends up, um, impacting ovarian function.

Dr. Beim: But also when the ovary is not signaling correctly, it can also Promote an environment where you have chronic inflammatory. Processes in your body and so this is why women become generally more inflamed. We know inflammation is related to weight gain

both: Yeah, we

Dr. Beim: know it's related to mental health issues.

Dr. Beim: It's related to cancer risk Generally to aging in an unhealthy way chronic inflammation is like a big red flag So the ovary is both impacted by inflammation, but also can impact inflammation We know that ovarian hormones impact inflammation. So this this During COVID one of my favorite examples, so polycystic ovary syndrome Yeah.

Dr. Beim: I have it. I've dealt with cystic ovaries throughout my life as well. So, um, PCOS, which impacts about 15 percent of all women, we have no disease altering treatments for it right now. Um, PCOS during COVID was an equivalent risk factor to having diabetes. We

Dr. Taz: didn't talk

Dr. Beim: about that. Nobody talked about it.

Dr. Beim: It's an ovarian health issue That created as much risk for women of having a really serious Effect of having COVID as diabetes and yet women with PCOS were not treated as high risk Because we don't think about the ovaries role in the immune system So that's really important and the metabolism is one of my favorites.

Dr. Beim: It's huge. Yeah, it's huge.

Dr. Taz: Talk to us about that.

Dr. Beim: Yeah, so so The ovary is in constant conversation with our metabolism, and you think about from an evolutionary standpoint, it makes sense. The ovary is the ultimate sensor. It checks in with the environment, and it says, um, Are we stressed out? Are we running from a tiger?

Dr. Beim: Is it wartime? Um, is this a safe time to bring forth our reproductive potential? Is this famine time? Is this winter? Is this summer? There are a number of signals, for example, um, light. There are mammals that are seasonal breeders, meaning just the small changes of light that happen in the winter completely shut their ovarian function down.

Dr. Beim: They cannot get pregnant in the winter. Just by sensing that the light has changed.

both: Wow.

Dr. Beim: So we are not seasonal breeders, but it doesn't mean we're completely not impacted by light either. And so, when you think about metabolic inputs, your diet, and whether there's food and whether there's nutritious food available to support the development of a pregnancy.

Dr. Beim: It's not surprising that it turns out that the ovary is this really beautiful detector of how we're doing on the nutritional front. But what that also means is it's going to impact your, um, your, uh, reproductive outcome. It's going to impact your ovarian function. And so people don't think about their diet impacting their ovarian function, or their declining or dysregulated ovarian function impacting their weight gain, their metabolism.

Dr. Beim: Um, I, I could get, I, I could science it and get into the insulin signaling and things like that. But, um, there's a reason why women find it harder to lose weight after a certain age.

Dr. Taz: Let's answer that for women because it's probably the number one question I get. Um, you know, and maybe A couple of science facts around that, like, you know, what exactly is happening?

Dr. Taz: You know, we know that estrogen is going down. We know progesterone is going down. What happens next?

Dr. Beim: Yeah. So, um, it's not just estrogen and progesterone. Those are important for metabolism, but there are actually dozens of factors that have already been identified and probably hundreds more because we haven't really looked for them all that directly impact insulin signaling.

Dr. Beim: So it's not even indirect through estrogen. It's actually, um, insulin growth factor. There's a number of, um, factors that are, um, either produced by the developing follicles, which are the cells that wrap around the egg. They're the cells, the follicle cells are the ones that do all the magic. And then the egg is in the middle.

Dr. Beim: Um, so those actually directly signal with all of the, um, you know, with your liver, with other aspects of your body, with your muscle. Um, this is why, for example, bringing back to PCOS or to perimenopause, um, when you put on muscle mass, when you have better, metabolic function in your muscles. For some women, it can impact their ovarian function.

Dr. Beim: The, um, Ozempic. Yeah, the

Dr. Taz: GLP1s. So, a number

Dr. Beim: of women have found that when they lose weight and they're on the Ozempic, they start ovulating

Dr. Beim (2): again.

Dr. Beim: And these are women who haven't ovulated regularly in years, maybe since puberty. Um, that's because that impact that the GLP1s are having, uh, the Ozempic type drugs are having on the metabolism.

Dr. Beim: Or signaling directly back to the ovary, but remember if there's something that can impact ovarian function It means the ovary is also impacting that function, right? And so that's why when you have an ovarian disorder like PCOS, polycystic ovary syndrome or you're in perimenopause and your ovarian functions are starting to shut down or you're in full menopause And most of your ovarian function has been depleted and is gone Not only are the signals not getting to a functioning organ, but they're not answering back.

Dr. Beim: And so, that beautiful symphony, bringing it back to the musical analogy, that beautiful symphony is, is, is leaving the, the biological, um, kind of system that your body has developed in and functioned under. This happens with men, too. They have decline in testicular function throughout their lifespan, but it's slow and steady.

Dr. Beim: More subtle, too, I think. It's more subtle, whereas with women, and, and there's biological reasons for this, but we have linear decline in our ovarian function throughout our, our early life, but then in what is now midlife, because we live until our, you know, 70s, 80s, you actually have a, not quite exponential, but a more than linear decline.

Dr. Beim: So you have this rapid, you know, they talk about falling off a cliff.

Dr. Taz: Yeah, yeah.

Dr. Beim: It's a horrible analogy because I think it feels so scary for people, but it actually looks like a cliff. If you look at how ovarian function declines, it accelerates. And we see that women who have a smoother line, and go into menopause more slowly and a little later, don't struggle with perimenopausal symptoms as much.

Dr. Beim: Not because their bodies aren't impacted, but because their bodies have time to adjust. And this is really important is that, in biology, fast change equals bad. This is why you want to lose weight slowly. You want to shift your sleep schedule slowly. You want to do anything that impacts your gut microbiome slowly.

Dr. Beim: Because that's how you get lasting change, and that's how you avoid stress, all of these things are also stress around your body. And so, um, men have the ability to adjust over time, women's bodies age like this. And so, that really helps explain it, and that gets back to my work in ovarian health, is that 100 years ago, we were not, on average, surviving past that cliff.

Dr. Beim: Right.

Dr. Taz: We were done.

Dr. Beim: We were done. Yeah. And, um, Now, we survive not just past that cliff, we survive decades. past that cliff. And so our ovarian function is not aligned with the modern human lifespan.

Dr. Taz: Right.

Dr. Beim: And my passion and, and my work, uh, especially over the last, um, six years has been really trying to change the shape of that trajectory.

Dr. Beim: So we can align ovarian function with our modern lifespan because we did so much to change our lifespan line, right? We used to do this. in our lifespan. Now we do this. And the ovary is the one organ that got left behind.

Dr. Taz: So I'm assuming this is where somatic steps into the conversation. Tell us about somatics.

Dr. Taz: Tell us what's happening there. And as a woman who is experiencing probably coming off that cliff, you know, uh, relatively soon, I can imagine, you know, what are our options? You know, is there a way to reverse our ovarian age? Is there a way to, you know, change things? And what does that mean for our longevity and for our overall health?

Dr. Beim: So we see ovarian health as one of the fundamental pillars, just like brain health, gut health, uh, metabolic health. And there's, there's two answers to that question. One is we don't have the tools really to do that today. And that's what we're doing at Cellmatics. We pioneered the category of ovarian health, but we also pioneered this idea that We should be leveraging therapeutics to intervene and allow us to exogenously, meaning, um, you know, outside of what's happening in the ovary, regulate the decline in ovarian function.

Dr. Beim: It turns out we're born with more function than we need, even in the modern lifespan. So in theory, if we could regulate how we use our ovarian function over our lifespan, our ovaries should align with the modern lifespan. And that's because the ovary also thinks it's a reproductive organ in many ways.

Dr. Beim: So it indexes on trying to create the perfect egg every single menstrual cycle. And, so we've heard of the menstrual cycle, which is this approximately 28 day cycle. Um, but what people don't realize is there's a bigger cycle. It's the folliculogenesis cycle. So we have like hair follicles, and our hair grows out of the hair follicles.

Dr. Beim: So we have ovarian follicles, and the egg grows inside those follicle cells. But those follicle cells, as I mentioned, are where a lot of the other functions, the non reproductive functions, lie. And, um, Because they're, they're kind of intertwined, the fate of the egg is wrapped up in the fate of the follicle.

Dr. Beim: You can't have a follicle without an egg. You can't have an egg without a follicle. So we're born with all the pre follicles and pre eggs that we'll ever have. And they're already kind of pre formed. They get signaled to start growing. And then they grow. And then, because we are not litter animals, we don't have litters.

Dr. Beim: We have typically one or maybe two per pregnancy. There's this fierce competition that happens during that process of folliculogenesis. It's a 300 day process to get from a pre follicle being activated to an egg being ovulated. The menstrual cycle is a 27 day finish line of what is actually a 300 day process.

Dr. Taz: Fascinating. Every

Dr. Beim: single therapeutic that we have in women's health only impacts the last 30 days. We have nothing that can impact the first 270. So how do you impact? The first 270 days, that's what we've been working on for going on 16 years soon. So first we had to understand what happens in the first 270 days.

Dr. Beim: And so we, we identified, we and others have identified that one of the key regulators of that process, that early process, um, is a hormone called anti Mullerian hormone. And anti Mullerian hormone is a fascinating hormone. in part because it was named for its role in male fetal development. So the mullerian system is the, um, early cell system that gives rise to the female tract.

Dr. Beim: So, you know, the fallopian tubes, the uterus, vagina, et cetera. And so in early development, we have the parts that can turn into You know male parts and we have the parts that can turn into female parts and you have these hormones that come on Kind of as the brakes and the accelerator in in male fetuses to say, okay suppress the female system and turn on the male system Mm hmm, and then in female fetuses, it's the opposite suppress the male and turn on the female And so it turns out that in male fetal development very high levels of anti mullerian hormone Are the signal to put the brake on the development of the female organs and this is why men don't develop fallopian tubes in a vagina And so, um, back in the 80s when everybody was obsessed about defining who is a female and who is a male for the Olympics, for children who were born with undetermined sex at birth, someone had the clever idea of, well, let's, let's find a test for anti mullerian hormone because it's literally the break to not be female.

Dr. Beim: And so, um, so. They developed a blood test for anti mullerian hormone and we're shocked to find that AMH, right? Everyone's staring at their labs. It's the AMH. Many women listening have probably been tested for AMH. So, the scientists were fascinated because all the women and girls they tested, tested positive for anti mullerian hormone.

Dr. Beim: How's it possible that a person walking around with a fully developed mullerian system has anti mullerian hormone? So, fast forward, it turns out that AMH is not only an ovarian hormone, it is the most fundamental regulator of folliculogenesis. And it serves as the brakes. It is what taps on the brakes to ensure that when, at puberty, we start turning on our folliculogenesis in a big way to start, you know, getting to an ovulated egg or oocyte at the finish line, um, that we don't do that too quickly.

Dr. Taz: So is this why in PCOS in our patients that we see AMH is high? That's right. That's right. Because the brakes are not working.

Dr. Beim: That's right. And also in, um, diminished ovarian reserve we see that AMH is low. Right. Because the brakes are not working in the other one. So

Dr. Taz: it's again that sweet spot.

Dr. Beim: That's right.

Dr. Beim: And so, um, with a lot of hormones it's a U shaped effect. So you don't want too much of it. You don't want too little of it, right? And this is really important. So, um, so what we realized is, wait, this male, the ultimate male hormone is actually the ultimate female hormone, which is very important. And always works out that way.

Dr. Beim: Yeah. So we need a rebrand. We need a serious, yeah, we need a rebrand. Um, but it turns out that in, in the laboratory with, um, animal models, um, with, um, kind of, you know, ovarian tissue that you've, um, put into culture. you can actually modulate the rate at which those pre follicles are recruited and develop.

Dr. Beim: And what we know is that To your point with PCOS, there are women who have so many follicles that there's a traffic jam, and it's kind of backed up. We have women who, um, don't have the ability to kind of exert the brakes, and they end up burning out their, um, their follicles too early, and experience early menopause, and experience other issues associated with that.

Dr. Beim: And so, what we found is that AMH, like many hormones, um, you can modulate it reversibly. So, and I've seen that in practice, by the way, you have,

Dr. Taz: yes, because we'll have patients come in, you know, with high AMH, a lot of the PCOS endometriosis population, or we have patients come in with low AMH and they've been told they have low ovarian reserve and they can't get pregnant.

Dr. Taz: Yeah. And then we work on these patients working on inflammation, oxidative stress, gut, you know, the whole holistic approach and the AMH changes. And, you know, they were like, well, my doctors told me that the AMH can't change. And I'm like, I, I am promising you, I've seen this number flip over and over again.

Dr. Taz: So now you're getting, you're the first person to give me some reasoning as to why, you know, other than what I kind of intuitively knew and what I was seeing on my lab work.

Dr. Beim: Yeah. Well, the ovary makes AMH says you change the ovary through these lifestyle. Remember we talked about. Inflammation can impact it, sleep, diet, because you're changing, like, as you're changing the ovary, you are changing AMH.

Dr. Beim: So it's not easy to modulate it, but you can modulate it. And, um, and so we want to make me not feel insane. I don't know how

Dr. Taz: many times I've had these conversations. It's not

Dr. Beim: all in your head.

Dr. Taz: I know! It's like, I am telling you these AMH levels change, and everyone's like, it's not possible. So, I feel so validated right now, so thank you.

Dr. Taz: That's awesome. But anyhow.

Dr. Beim: Awesome. So that's what we're trying to do from a therapeutic standpoint is we're trying to create a drug that mimics AMH because unlike estrogen and progesterone and testosterone, you can't synthesize AMH in a lab. It's a huge molecule. It's a very, very large molecule, um, and you also can't grow it in a petri dish, which you can do with like, for example, injectable fertility drugs.

Dr. Beim: Those are also very large molecules, but you can make them in cell systems. AMH, we won't get into it, but let's just say because it is such a master regulator, it was, it has evolved, the hormone itself has evolved to not want to be at very high levels in your bloodstream because it is so potent.

both: Mm hmm.

Dr. Beim: And so the challenge, and we actually, Super proud. We were the only company to be chosen for a spark award as part of the Women's Health Initiative. The Biden administration, um, uh, directed ARPA H, this incredible new, um, innovation engine within the U. S. government for health, uh, innovation to, um, to help accelerate, uh, at warp speed, uh, women's health.

Dr. Beim: And so we were selected for our AMH therapeutic program to develop A drug that can be produced and and and you know, um made as a drug but that mimics the action of AMH so that we can start to modulate it and the idea is that We don't want it to be the lottery like my body can regulate my ovary effectively or it can't we actually want to democratize We want to give access to women To all be able to regulate their ovary in the way that is best for their lifespan and their longevity.

Dr. Beim: And it's going to mean a lot of things. So, I mean, we could talk about this for hours, but a couple of things, because a couple of common fears that people have when they hear that we're going to do this. So, well, um, you know, what's going to happen if I don't have all those follicles? For women with PCOS, we predict it's going to be awesome for them.

Dr. Beim: They're going to have a normally functioning ovary, because they're not going to have this follicle traffic jam, where none of the follicles can break free and get to that. And would it extend our ovarian age? That's the hope.

Dr. Taz: Okay. That is the hope. Because you don't have the traffic jam, and so you're not burning out the ovary.

Dr. Taz: And you're

Dr. Beim: not prematurely. Right. So, you know, there's a lot of variation, whether some women recruit a few follicles a day, some women recruit hundreds of follicles a day, and there's no way to modulate that right now. And so what's nice is that, just like the birth control pill and being able to use estrogen and progesterone, can give most women a 28 day cycle that's predictable.

Dr. Beim: less pain with their periods. Um, and that's something that we can regulate with drugs, right? We want to give everyone a nice follicular genesis cycle too. So we want to personalize follicular genesis so that we're only pulling how many follicles we need out of storage day over day. For our health. What that means is we're not going to make the perfect egg every month.

Dr. Beim: But the reality is most women don't need a perfect egg every month. Right. What they need. That's a lot of kids. Yes. We're already taking contraceptives or taking measures to avoid getting pregnant. So for women what this means is fewer periods.

Dr. Beim (2): Mm hmm.

Dr. Beim: From a frequency standpoint, but spaced out longer throughout their lifespan, which actually mimics Natural biology better because the way that we live right now is is not natural,

Dr. Taz: right?

Dr. Taz: We were meant to we weren't meant to have this

Dr. Beim: many periods. Yeah, we would get pregnant We would have extended periods of breastfeeding which suppresses those hormones So taking a major over a lifespan, this is all what we're aiming towards this hasn't been tested obviously, we're still developing this but the theory at least that we're going after is that if we could If we could modulate ovarian folliculogenesis by having a drug that mimics the action of AMH, then we could get to that personalized sweet spot for each woman so that she has the optimal ovarian health for decades longer than she has right now.

Dr. Beim: Because a lot of women say, like, well, I mean, yeah, I have all these perimenopausal symptoms, or I have osteopenia, or osteoporosis, or heart disease, or all these things, but like, thank God I don't have PMS anymore. Thank God I don't have to deal with these heavy, frustrating periods, and mood swings, and all these things.

Dr. Beim: But the point is that, I'm not saying let's take all the awful ovarian biology you've had to live through, and make you live through it forever. That's not what I'm saying. I'm actually saying, let's give you optimal ovarian health, and then have that extend. Um, for decades longer than it does right now, it's a complete rewrite of how we think about women's health and women's bodies.

Dr. Beim: And um, I think about my daughter who's seven right now and she asks me, you know, all the time, mommy, are your medicines going to be ready in time for me? And it's, it's so sweet. And it's also tough, you know, because it takes 10 years, you know, and I do the math of like, well, you're going to get your first period, you know, seven years and, um, but I, I really, truly believe that, um, my daughter, her generation.

Dr. Beim: You know, I think the technology we're developing is going to impact women who are probably in their late 20s right now, maybe early 30s. We'll have it ready in time. But really for women who are in their early 30s and younger, they're gonna look back on this, let's call it century of human history, where we Extended the human lifespan, but not the ovarian lifespan.

Dr. Beim: We didn't figure out how to modulate ovarian function, but we added contraception to the mix, so women just had period after period after period. And they're going to look back on this, on this kind of microcosm of the century before we figured it all out, and just be baffled as to how we all thought this was okay.

Dr. Beim: Yeah for us to all feel this way during our prime years and then to not thrive necessarily physically in certain ways after what is now Midlife because I think for women of my daughter's generation They are gonna have much better functioning ovaries a lot of these things like PCOS endometriosis PMS these are gonna be anachronisms This is gonna be something that happened to women last century and that we just accepted And I also think that they're gonna be shocked that we just went into menopause Didn't do anything about it and also that we did nothing to optimize our ovarian health.

Dr. Beim: I think about like these stories about you know, figures from the past, um, George Washington, you know, with his teeth, you know, or people who had wooden teeth. And it's just, we cannot relate to a world in which we didn't care for our oral hygiene. We didn't go to the dentist. We didn't optimize the function of our teeth.

Dr. Beim: If we lived our lives vis a vis our oral hygiene, like we used to, our teeth would fall out in midlife. Right. But now they extend well and we've aligned. The longevity of our teeth. We need

Dr. Taz: to do the same for the ovaries. Yeah, the ovaries and

Dr. Beim: we could keep saying this over and over again. We know what we need to do to keep our brains healthy.

Dr. Beim: We know what we need to do to keep our teeth healthy, our bones healthy. Most people don't know what they need to do to keep their ovaries healthy.

Dr. Taz: So, you know, is there anything women listening today can do right now? To optimize their ovarian health while we're waiting for these drugs of the future, right?

Dr. Taz: That are gonna hopefully help us to even out the lifespan of our ovary, you know, what could they do today?

Dr. Beim: So a number of things. Um, so I have a I have an Instagram page now, Boss Ovary. Boss Ovary. Let's check it out. Everyone go there. This is not my comfort zone. I am very much a, the lab is my happy place.

Dr. Beim: Um, but I am trying to get the word out because there are things that you can do and I'm trying to put more and more content to help women understand. These are things that I've started to do for myself as well. And I've found that my ovarian aging has At least anecdotally for me, my AMH levels have barely changed over the last five years, which has been awesome.

Dr. Beim: Um, and, um, so, um, so a couple of things. One is that you can avoid the things that will shorten the lifespan you already have for your ovary. So everybody has a hardwired lifespan based on, ovarian lifespan, based on how many follicles are born with at birth. And their, their intrinsic genetics of how that ovarian timer, people talk about the biological clock, but it's more of a timer.

Dr. Beim: So it's kind of a, a countdown. And so, everybody has, let's say, the optimal, uh, longevity that their organ can have based on their, their genetics and, and what they were born with. And so what we can do is we can avoid the things that, That Chinese

Dr. Taz: medicine concept of, you know, here's the chi you're gifted with, it's your job now, grow it or deplete it.

Dr. Taz: That's right.

Dr. Beim: So I think there are things that definitively have been demonstrated to deplete it. So one is smoking. One is smoking. That also means exposure to environmental toxins that are like smoke. So a simple thing that I've incorporated into my household, which also benefits the My whole household, not just my ovaries, is just a very high quality air purifier.

Dr. Beim: Yeah, it is. It is just a no brainer. I think, especially if you live in a city, um, we have wildfires. We just had a wildfire in the heard. I heard. Yeah, I think, especially with global warming, we have these moments where air quality, um, you know, is, is not just in places like China, where we hear about this in the U.

Dr. Beim: S. as well. Periodically, we have real air quality issues, getting a very high quality, uh, air purifier, really controlling that, your indoor air quality, sometimes just, Um, like I try to open my windows. Yeah. A couple minutes every day. So, I think keeping track of, um, the air that you are breathing, including avoiding things like smoking, is super important.

Dr. Beim: Um, the other thing is that, um,

Dr. Beim: diet, lifestyle factors related to inflammation are important. Mm hmm. So generally, one of the processes that can impact ovarian aging is, um, fibrosis. So this is when tissue becomes fibrotic. Um, and for a number of women with PCOS, their ovaries actually become so fibrotic from all those back that traffic jam of follicles, um, that it starts to actually kill their ovary.

Dr. Beim: And about 15 percent of women who have PCOS early in life go into very early menopause. It's not true. Most women with PCOS go into later menopause slightly. But some women actually fall off a cliff much faster. And it's because they have all this fibrosis. So what I would say is that if you're struggling with obesity, if you're struggling with chronic inflammation, You are, you are accelerating the, um, underlying aging mechanism, not only of your body, but your ovary, and that ends up being kind of a, your ovary ages faster than your body ages faster.

Dr. Beim: It ends up kind of that. So I would say that, um, manage those lifestyle factors for

Dr. Taz: sure. What about light? You mentioned light. And I'm just thinking about all the people on their phones and the blue light that we have nowadays. Is that Is that something we should be a little bit more mindful of or is that a little bit lower on the list?

Dr. Beim: You know, it's I'm very mindful of it because now I'm in perimenopause and I think that So that's kind of a slightly different category if we're talking about what you can do to extend ovarian function and optimize ovarian function I think being You know, careful about the environmental toxins that you're putting into your body because your ovary is one of the most sensitive organs in your body.

Dr. Beim: Levels of radiation that won't impact anything else in your body will start to kill your ovary ovary is one of the first things that starts to be impacted by toxins. And, um, and, and, you know, uh, things like radioactivity. So, you want to, uh, you want to be careful, um, about things like that. I think that when we think about, um, what women can do, Once they start to approach perimenopause or if they have ovarian dysfunction and they have ovaries that are more sensitive or not as hardwired to function correctly, um, is they have to control the things that are being dysregulated.

Dr. Beim: If you have an ovary and it's working in perfect harmony with the rest of your body, that's great. You can take on some extra risk factors, right? This is kind of like when you're, um, when you're younger and in general you haven't started the mechanisms of aging as much, you can have a later night, you can have that extra glass of wine, you know, you can handle the stress.

Dr. Beim: As we get older, you can't handle it as well. So the same thing is true for your ovary. So when you think about, um, okay, my ovary is not functioning as well. Um, I wear a continuous glucose monitor. Mm hmm. Me too. You do? Okay. Awesome. Um, I started wearing one back in 2020. Yeah. When we started to see the, the interplay between, uh, the ovary and metabolism.

Dr. Beim: Um, and I have found that it's a game changer for things like hot flashes. Mm hmm. Right? Like, one of the things that concerns me about these drugs that are specifically targeting the thermostat and the brain is that it's like the house is on fire, and instead of dealing with the house being on fire, you just turn the fire alarm off, and you go back to sleep.

Dr. Beim: And, for women who have debilitating hot flashes, they've gotta just get some sleep, you know, do whatever they can to turn the thermostat off. I'm not coming out anti these drugs, I'm just saying Take the drugs, manage the hot flashes, but don't forget why you're having the hot flashes. And what I have found is that when I'm being really disciplined about the lifestyle factors that do impact my ovarian function, then I don't get the hot flashes, I don't get the perimenopausal symptoms in the same way.

Dr. Beim: And so I encourage women whose ovaries are either not functioning anymore because they're menopausal, or are functioning less well because they're perimenopausal or they have conditions like PCOS to be very mindful about light exposure. So that means getting adequate sleep because sleep is a time when you make melatonin.

Dr. Beim: Melatonin is your sleep hormone. And you cannot make ovarian hormones without melatonin.

Dr. Beim (2): The ovary will stop

Dr. Beim: functioning. If you stick a mouse in all dark or all light for two weeks, it stops ovulating. It gains weight. It becomes insulin resistant.

Dr. Taz: Wow. Yeah. Oh my gosh. I'm not a good sleeper. That's all it takes.

Dr. Taz: I'm

Dr. Beim: always trying to cheat. So anyhow. And we know from IVF related studies that, for example, when they look at nurses who have shift work and they work at night, they have much lower IVF success rates as well because their ovaries are being impacted. It's impacting their egg quality. It's impacting their health.

Dr. Beim: And so, um, I think, yes, sleep's a big one. And unfortunately that means the screens. Right. The screens are a big one. Um, we see that in cities like New York, um, where children weren't able to get outside during the pandemic and we're on screens all the time. Overnight, we had a, I think, uh, an increase from 5 percent precocious puberty, meaning girls going into puberty before the age of 8, to like 20%.

both: And that's from light. That's from light. Oh my gosh, we've been seeing this. Yes,

Dr. Beim: because their little ovaries were so impacted by missing out on the normal circadian rhythm, being blasted by blue light. Hasn't been proven, but that's what's been hypothesized. And based on what I've seen in our work, I really believe that hypothesis that the disruption of melatonin.

Dr. Beim: So for my kids, we talk about melatonin.

Dr. Taz (2): Right.

Dr. Beim: Not because they take it as a supplement. I don't give my kids melatonin, but um, but we talk about melatonin like it's night time as we approach the evening, we start to dim the lights if they need to do homework, we do it with a task light rather than having all the lights on and and the kids are mindful.

Dr. Beim: Oh, I don't want to see a screen right now. I don't want to wreck my melatonin. My brain has to start getting me ready to keep me asleep so that I can make more melatonin. And then what melatonin does is it has powerful anti inflammatory impacts. Thanks. It allows us to metabolize the food that we ate in a better way.

Dr. Beim: Melatonin is not just a sleep hormone, it's also a metabolic hormone, it's also an ovarian hormone. And so When you're losing that signaling from the ovary, your melatonin signaling starts to be disrupted. So you have to practice good sleep habits, but that also means, um, part of good sleep habits are exposing yourself to the right kind of light at the right times.

Dr. Beim: So on my Instagram, I'm always posting, like, me outside in the sun, or my kids outside in the sun, like, we have a rule at home on the weekends, you 11, rain or shine. So, I have rain gear for my kids, I have snow gear for my kids, like rain or shine. You have to be outside. You have to be outside. Wow. Without sunglasses on, before 11 in the morning, to just tell your brain, we're awake.

Dr. Taz: Yeah. Oh my gosh, this is so fascinating. I could talk to you about this. I have more questions. I don't know how to get all my questions in. I have so many more questions. I mean, I'm so curious. We'll probably have to do a part two. What you think about, you know, fertility today and the you know, the whole assisted reproduction and sort of what your opinion is on, on that industry, what you're hoping for women in perimenopause and menopause, you know, someone who's going into menopause, like can they bring their AMH back up?

Dr. Taz: Have you seen that happen? Is that a possibility?

Dr. Beim: Um, I think that it's hard. Um, once you were, you can bring it up on a short term basis, like you said, through some of these interventions, I think that, um, it's more about. I think giving your ovary the best shot to age on the best trajectory possible. So I did all the wrong things from an ovarian health standpoint when I was younger.

Dr. Beim: Um, I smoked. I was chronically sleep deprived. I, I lived off of like Snickers bars and, and Coke. I have such a healthy lifestyle now when people hear about my lifestyle when I was in graduate school. Right there with you. Yeah. Diet Coke, Diet

Dr. Taz: Coke and popcorn. Those were my go to's.

Dr. Beim: Yeah, yeah. So we, we did not fuel our bodies.

Dr. Beim: No. We did not rest our bodies. So I, I did all the wrong things when I was younger. Yeah. And I, and I had the sobering, um, realization in my early thirties that I had very low AMH. And so. Based on my AMH levels, I should have gone into menopause, um, by around 40. Mm hmm. I'm now, uh, turning 46, uh, very soon, and my, since I changed my lifestyle, my AMH levels have barely changed.

Dr. Beim: Wow. It's been incredible. That's incredible. Because I, I really grieved when I got that diagnosis early in my 30s. I thought, um, well, that's it. You know, I, I, It, you know, this didn't work out for me and, um, I'm not going to be able to have children naturally. I'm not going to, I mean, I was actually counseled that IVF wasn't going to work for me.

both: Oh my gosh. Yeah.

Dr. Beim: But I was trashing my body. I really was not taking, I mean, not like drugs and alcohol, but like, you know, all the other lifestyle factors, I was not doing well for my body. And I, I made so many changes. The other thing that, um, you know, from an ovarian health standpoint that I think is worth mentioning is endometriosis.

Dr. Beim: So, endometriosis, we think of it as a menstrual disorder. Um, women often have very painful periods, so we associate endometriosis with menstruation. But, um, what we know is that AMH, uh, levels can impact endometriosis risk. And that having endometriosis can impact ovarian health as well. So there's a circle there.

Dr. Beim: And what I would say is that, um, For women, that impacted me. I have endometriosis and that's part of why I had lower AMH by my early 30s is that that also went untreated. Um, it was in part because pain was normalized for me. When I had my first endometriosis symptoms, which was my very first period, um, I mean I'd never been in pain like that in my life.

Dr. Beim: And now that I've had the opportunity to, uh, deliver babies and go through labor, what I learned was that A typical period for me, if I was unmedicated, felt like transitional labor.

Dr. Taz: Wow. I mean, I just think there's so much here that is It's actually a message of hope, to be honest, you know, like, first of all, drugs that your company is developing and working on.

Dr. Taz: I think that's, you know, I have a 16 year old, I think about her health all the time. So for our girls and for young women, you know, it's super exciting that they'll be able to have better control of this. I feel like we've had to fight for it or have had to learn it by bumping our heads around. So I think that's really hopeful.

Dr. Taz: I think the other hopeful and I think call to action for all women listening, and I hope they pass this on to their daughters and their mothers and their sisters and whoever else is, let's follow these numbers, right? Why can't we follow an AMA? I do this in practice, but it should be standard. Follow your AMH, follow your inflammation markers, understand what's happening, no matter how old you are, because it's your first window really into not just your overall health, but now like your ovarian health, which is an important piece of.

Dr. Taz: of everything. Everything's bi directional. So I think that's a really important message I hope people will take from our conversation as well. I'm super excited about the work you're doing. Look, I could talk to you for probably another hour and I'm already getting time signals from everyone, but I want to leave with just one question that I'm asking all my guests.

Dr. Taz: You know, you are a pioneer in your field. field. You're a pioneer in this area of ovarian health. You founded cellmatics. You've been recognized globally as an entrepreneur and an innovator. I've read your bio. You've done so many amazing things. Just thinking about what gets you up in the morning and what keeps you going.

Dr. Taz: I want to know what makes you whole.

Dr. Beim: Oh my gosh. Um, well, I'm a mom and so I'll just lead and say that my children inspire me. I really, really want a different world for your daughter, for my daughter, but also for my boys. It's so important. And, um, if you ask my, my boys, what does mommy do? They say, well, Our testes are going to function throughout our lifespan, but our sister's ovaries are going to stop working in the middle of her life, and that's not fair.

Dr. Beim: Mommy's trying to do something about it. Amazing. I think it's like if you can explain it to a five year old, so it's pretty simple. It's an equity issue. And, um, so, so they're rooting for me, and I don't want to let them down. And I want to show them that. Um, that you can put your mind to hard things that feel impossible.

Dr. Beim: Everything starts with a dream. Everything starts with a crazy idea that you have, and then you can add data to it. You, you know, science is real. And so I'd say that, that being that role model for my children, but also that facilitator, that catalyst of a better health outcome for them, is really important to me.

Dr. Beim: But the other thing that I will say is that I barely go a week. And I've been at this, you know, for over 20 years, as I mentioned, without somebody sharing, um, the fertility struggle they're having. Uh, just last week I got three phone calls from women in my network because they had been counseled to remove parts of their body, their fallopian tubes, their uterus, their cervix, their ovary.

Dr. Beim: And, um, and, and I reflected on it that, While men do, of course, lose body parts, not at the frequency that women do. I mean, the, the fact that we don't understand female biology, we don't know how to treat female biology, and so then as we start to accumulate diseases because of female biology, we just neutralize the female biology, remove the parts, kill the estrogen.

Dr. Beim: The fact that that's our toolbox. I am constantly reminded. It drives me insane. It drives me insane too, and, and I, I will be honest, because I think sometimes you can make it look easier than it is. Um, having this conversation, this is my happy place, getting to talk about this stuff. I'm very passionate about it, but I will say, I want to give up every single day.

Dr. Beim: Every single day. It's a fight. Every single day. There's a moment where I think it's too hard. It's not gonna work. People aren't gonna understand We're not gonna have adequate funding Some setback every day makes me think I'm exhausted. I you know, who am I one person? Every day if I'd be lying if I didn't say for a minute at least every day some days it's hours some days It's just that minute of can we do this?

Dr. Beim: Are we gonna get this done? I doubt myself every day, and when I get that phone call from a friend who says you'll never believe what my doctor said to me.

Dr. Taz: The fire starts right back up. Boy,

Dr. Beim: or my daughter says, you know, tick tock. Yeah. You know.

Dr. Taz: Get on it, mom.

Dr. Beim: When is this stuff going to be ready? You know, or it feels just so obvious to my boys that of course we should live in a world where our sister has the same rights.

Dr. Beim: to have her body age on the same trajectory that we have. Um, and let me end with one statistic, too, because oftentimes people say, well, women outlive

Dr. Taz (3): men.

Dr. Beim: Aren't you, you're more than equal. Statistically, yes. But we don't outthrive men. Right. We are sick for 25 percent longer. So, that's my answer to that, is that when I talk about aging equitably, and enabling that.

Dr. Beim: Um, what I mean is WellSpan. The years that we feel healthy, the years that we can run a triathlon, the years that we can think clearly and, and be our most creative, passionate selves, that we have a sex drive, that we, um, you know, don't have all of the issues that, as you know, and your audience knows, we struggle so much with once our ovaries start to go offline.

Dr. Beim: So Those are the things that inspire me is that, um, we have a real shot at this. I mentioned we got the ARPA H SPARC award for ovarian health. And, and now we have the U. S. government as our strategic partner in this. They've recognized ovarian health matters to the health of the nation. And, um, so I'd say it's getting a little easier.

Dr. Beim: But, um, but moments like this to inspire me where, um, people are getting excited about our work and, and starting to figure out like while they're rooting us on for the exciting things that we're going to do for the next generation. What the, what we learn about biology on the path to creating those new innovations gives us these tools like we were talking about diet, lifestyle, sleep, stress management, exercise.

Dr. Beim: That we can do today to at least make the most of what we have.

Dr. Taz: I think this is such an incredible journey. I'm gonna be rooting and cheering you from the sidelines for sure. And I do think that, you know, what makes a lot of us whole, honestly, is the ability to really make that impact, right? To have that stamp on the world and be able to say that we created something, did something that really did change lives at the end of the day.

Dr. Taz: I know I feel the same way. There are days that I'm like, why am I doing this? Like what is wrong with me? But it is, it's the stories and it's the experiences that again, we get faced with over and over again. They keep us all motivated. So you're an inspiration. I'm so proud to know you. I am, I have been inspired by this conversation.

Dr. Taz: So thank you for taking time out today to join us. And I know you mentioned boss ovary is a place where people can find you on social media and follow you. Is there anywhere else that, you know, if they're curious about your work, that, uh, they can go and learn more.

Dr. Beim: Well, they can follow us. We're actually, um, we're pretty good on LinkedIn.

Dr. Beim: Yep. So somatics is pretty good on LinkedIn about talking about our updates. So we had, um, some recent. breakthroughs we didn't get a chance to talk about. For example, we're trying to get rid of needles from IVF and just create a world where we can both reduce the need for IVF through treating fertility more effectively at the OBGYN, but also getting rid of needles when we get there.

Dr. Beim: So there's a lot of other things other than, um, What we talked about today that we're working on. And if people are interested in our work at Selmatics, they can follow us on LinkedIn or on our website, Selmatics. com. And then, um, and then I'm trying to be pretty good on boss over you too, of as I learned things and I'm, this is why I started at a friend of mine in media said, you, you figured this protocol out for you.

Dr. Beim: You're doing it for you. Just throw posts on and take us along on the journey. And so I've been trying. to do that, but also in the context of showing people the ups and downs of being an entrepreneur in this space as well, because I think that a lot of people didn't realize that so little capital goes into innovation in this space, so that's what I'm trying to do with Boss Ovary right now.

Dr. Taz: Amazing. Well, thank you again for joining us and for everybody watching and listening. I hope you'll check her out and check out all the resources and let's all advocate for ovarian health and help women understand this really important issue. Thank you so much.

Dr. Taz (3): Thank

you.

How Ovaries Influence More Than Just Reproduction with Dr. Piraye Beim
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